Chromosomal proteins appear to have an important regulatory function in the control of transcription. The nonhistone proteins and their phosphorylated derivatives may serve as positive regulatory agents. Intrinsic nuclear protein kinases (and phosphatases) appear to be involved in these phosphorylation reactions. Marked early changes in nuclear protein kinase reactions in rat ventral prostate have been observed in response to varying androgenic status. Initial studies on prostatic nuclear kinases indicate that while androgen deprivation causes a rapid differential decline in activity of some nonhistone protein kinases, the activity of one such enzyme (low in the normal) appears to significantly increase. Experiments are proposed to isolate and characterize these enzymes, determine their localization, identify their substrates among the prostatic nuclear proteins, and examine their control by androgen. The observation that polyamines in vitro differentially enhance the phosphorylation of chromatin-associated proteins, will be expanded to identify those nonhistone proteins which are more highly phosphorylated in the presence of spermine in vitro. For these studies, chromatin from normal and castrated rat prostate will be used. Further, it is proposed to determine if the androgen-sensitive specific "spermine-binding" protein influences polyamine action on protein phosphorylation. Experiments are also designed to determine if nuclear nonhistone basic proteins which bind 3H-DHT-receptor complex can undergo phosphorylation, and if so, to determine whether or not there is a subsequent effect on their acceptor activity. The proposed studies may contribute to our understanding of the factors that govern the "target" function of testosterone. Because of the absence of accepted experimental models of human prostatic neoplasia, it is also proposed to compare the nonhistone proteins, and their phosphorylated derivatives and associated protein kinases in nuclei from normal, hyperplastic and cancerous human prostate. It is hoped that the results will uncover differences in these parameters between normal and abnormal human prostate which might potentially increase our understanding of the etiology and treatment of prostatic cancer.